Krueger 2002

Methods	RCT, placebo‐controlled, double blind Date of study: 21 November 1999‐22 March 2001 Location: 51 centres in USA/Canada
Participants	Randomised: 553 participants analysed (mean age 45 years, 387 male) out of 569 patients randomised Inclusion criteria Participants with moderate‐severe psoriasis (BSA ≥ 10) Age ≥ 16 Non‐response to phototherapy Non‐response to conventional systemic treatment Exclusion criteria Pregnancy Had an active infection Dropouts and withdrawals 79/569 (10%) 16 excluded from analysis: 7 at 1 site because of poor compliance and 9 who were not dosed 9 lost to follow‐up: alefacept (3), placebo (6) 13 disease worsening: alefacept (8), placebo (5) 8 AEs: alefacept (7), placebo (1) 29 by request: alefacept (10), placebo (19) 4 other; alefacept (3), placebo (1)
Interventions	Intervention A. Alefacept (n = 367), IV, 7.5 mg, once a week, 12 weeks Control intervention B. Placebo (n = 186), IV, once a week, 12 weeks
Outcomes	Assessments at 14 weeks Primary or secondary outcomes of the trial PASI 75 Outcomes of the trial PGA clear or almost clear PASI 50 AEs
Notes	Funding source, quote (p 821): "This study was funded by Biogen, Inc, Cambridge, Massachusetts" Declarations of interest p 821): "A patent on the use of alefacept for the treatment of psoriasis has been assigned to Biogen and the University of Michigan. None of the authors have a financial interest in the patent. Gerald G. Krueger, MD, Kim A. Papp, MD, and Charles N. Ellis, MD, are consultants to Biogen, as well as to other companies that have and are developing treatments for psoriasis."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote (p 822): " This was a randomised..." Comment: no description of the method used to guarantee random sequence generation
Allocation concealment (selection bias)	Unclear risk	Quote (p 822): " This was a randomised..." Comment: no description of the method used to guarantee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 823): “... The active drug and placebo were visually indistinguishable from each other, and the injection volume was consistent. Physician who had no contact with the patient, … A pharmacist who had no contact with the patient…. The physician and the pharmacist were instructed not to communicate any information to the examining physicians….” Comment: use of a placebo with no major side effects
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 823): "An examining physician administered the study drug" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	569 included/557 analysed (comment: 16 participants excluded, 7 because of poor compliance and 9 were not dosed) Quote (p 825): "Analyses of efficacy end points ... were based on the intent‐to‐treat population, which included patients who were randomised had a baseline assessment and had at least 1 injection" Methods for dealing with missing data: not stated Comment: not modified ITT (7 participants excluded because of poor compliance) however 7/557 low rate
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available. The pre‐specified outcomes mentioned in the methods section appeared to have been reported